Unknown

Dataset Information

0

A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues.


ABSTRACT: The vertebrate T-box transcription factor gene Tbx18 performs a vital role in development of multiple organ systems. Tbx18 insufficiency manifests as recessive phenotypes in the upper urinary system, cardiac venous pole, inner ear, and axial skeleton; homozygous null mutant animals die perinatally. Here, we report a new regulatory mutation of Tbx18, a reciprocal translocation breaking 78kbp downstream of the gene. 12Gso homozygotes present urinary and vertebral defects very similar to those associated with Tbx18-null mutations, but 12Gso is clearly not a global null allele since homozygotes survive into adulthood. We show that 12Gso down-regulates Tbx18 expression in a manner that is both spatially- and temporally-specific; combined with other data, the mutation points particularly to the presence of an essential urogenital enhancer located near the translocation breakpoint site. In support of this hypothesis, we identify a distal enhancer element, ECR1, which is active in developing urogenital and other tissues; we propose that disruption of this element leads to premature loss of Tbx18 function in 12Gso mutant mice. These data reveal a long-range regulatory architecture extending far downstream of Tbx18, identify a novel and likely essential urogenital enhancer, and introduce a new tool for dissecting postnatal phenotypes associated with dysregulation of Tbx18.

SUBMITTER: Bolt CC 

PROVIDER: S-EPMC4104242 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

A distant downstream enhancer directs essential expression of Tbx18 in urogenital tissues.

Bolt C Chase CC   Elso Colleen M CM   Lu Xiaochen X   Pan Fuming F   Kispert Andreas A   Stubbs Lisa L  

Developmental biology 20140520 2


The vertebrate T-box transcription factor gene Tbx18 performs a vital role in development of multiple organ systems. Tbx18 insufficiency manifests as recessive phenotypes in the upper urinary system, cardiac venous pole, inner ear, and axial skeleton; homozygous null mutant animals die perinatally. Here, we report a new regulatory mutation of Tbx18, a reciprocal translocation breaking 78kbp downstream of the gene. 12Gso homozygotes present urinary and vertebral defects very similar to those asso  ...[more]

Similar Datasets

| S-EPMC8284783 | biostudies-literature
| S-EPMC4558550 | biostudies-literature
| S-EPMC2386664 | biostudies-literature
| S-EPMC2887422 | biostudies-literature
| S-EPMC2409229 | biostudies-literature
| S-EPMC4868469 | biostudies-literature
| S-EPMC3739036 | biostudies-literature
| S-EPMC4266991 | biostudies-literature
| S-EPMC1592840 | biostudies-literature
| S-EPMC1446946 | biostudies-literature